Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs.
Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs.
复制标题
人类基因组的普遍转录产生数千个先前未识别的长基因间非编码RNA。
DOI：
10.1371/journal.pgen.1003569
复制
发表时间：
2013-06
期刊：
影响因子：
4.5
通讯作者：
McManus MT
中科院分区：
文献类型：
--
作者：
Hangauer MJ;Vaughn IW;McManus MT
已知的蛋白质编码基因外显子占人类基因组的不到3%。剩下的97%在很大程度上是未知的领域，只有一小部分特征。最近的观察转录在这个基因间的领土刺激辩论的程度，基因间转录，这些基因间RNA是否是功能性的。在这里，我们直接观察到大量的RNA-seq数据，涵盖了广泛的人类组织类型，大部分基因组确实被转录，证实了ENCODE项目最近的观察结果。此外，使用这种RNA-seq数据的从头转录组组装，我们发现基因间区域编码的基因间非编码RNA（lincRNA）比以前描述的要长得多，这有助于解决大量观察到的基因间转录与有限数量的以前已知的lincRNA之间的差异。总的来说，我们鉴定了数以万计的推定的lincRNA，其以每个细胞至少一个拷贝表达，在先前的lincRNA注释集上显著扩展。这些lincRNA是特异性调节和保守的，而不是转录噪音的产物。此外，lincRNA强烈富集性状相关SNP，表明基因间性状相关区域可能发挥作用的新机制。这些发现将使新的基因间功能元件的发现和审讯。人类基因组的大部分是由基因间序列组成的，即基因之间的区域。基因间序列曾被认为是转录沉默的“垃圾DNA”，但最近发现基因间区域可以转录。然而，这种基因间转录的范围，性质和身份仍然未知。在这里，通过分析大量的RNA-seq数据，我们发现>85%的基因组被转录，这使我们能够生成一类重要的基因间转录物的全面目录：长基因间非编码RNA（lincRNA）。我们发现基因组编码的lincRNA比以前已知的要多得多。该领域的一个关键问题是这些基因间转录本是功能性的还是转录噪音。我们发现，我们鉴定的lincRNA具有许多与噪声不一致的特征，包括其表达的特异性调控，保守序列的存在和受调控加工的证据。此外，这些lincRNA强烈富集了先前已知在人类性状和疾病中起作用的基因间序列。这项研究提供了一个重要的框架，从中可以识别和表征基因间区域的功能元件，促进未来的努力，了解基因间转录在人类健康和疾病中的作用。
Known protein coding gene exons compose less than 3% of the human genome. The remaining 97% is largely uncharted territory, with only a small fraction characterized. The recent observation of transcription in this intergenic territory has stimulated debate about the extent of intergenic transcription and whether these intergenic RNAs are functional. Here we directly observed with a large set of RNA-seq data covering a wide array of human tissue types that the majority of the genome is indeed transcribed, corroborating recent observations by the ENCODE project. Furthermore, using de novo transcriptome assembly of this RNA-seq data, we found that intergenic regions encode far more long intergenic noncoding RNAs (lincRNAs) than previously described, helping to resolve the discrepancy between the vast amount of observed intergenic transcription and the limited number of previously known lincRNAs. In total, we identified tens of thousands of putative lincRNAs expressed at a minimum of one copy per cell, significantly expanding upon prior lincRNA annotation sets. These lincRNAs are specifically regulated and conserved rather than being the product of transcriptional noise. In addition, lincRNAs are strongly enriched for trait-associated SNPs suggesting a new mechanism by which intergenic trait-associated regions may function. These findings will enable the discovery and interrogation of novel intergenic functional elements. Much of the human genome is composed of intergenic sequence, the regions between genes. Intergenic sequence was once thought to be transcriptionally silent “junk DNA,” but it has recently become apparent that intergenic regions can be transcribed. However, the scope, nature, and identity of this intergenic transcription remain unknown. Here, by analyzing a large set of RNA-seq data, we found that >85% of the genome is transcribed, allowing us to generate a comprehensive catalog of an important class of intergenic transcripts: long intergenic noncoding RNAs (lincRNAs). We found that the genome encodes far more lincRNAs than previously known. A key question in the field is whether these intergenic transcripts are functional or transcriptional noise. We found that the lincRNAs we identified have many characteristics that are inconsistent with noise, including specific regulation of their expression, the presence of conserved sequence and evidence for regulated processing. Furthermore, these lincRNAs are strongly enriched with intergenic sequences that were previously known to be functional in human traits and diseases. This study provides an essential framework from which the functional elements in intergenic regions can be identified and characterized, facilitating future efforts toward understanding the roles of intergenic transcription in human health and disease.
登录
查看更多内容
影响因子：
56.9
作者：
Cheng, J;Kapranov, P;Gingeras, TR
通讯作者：
Gingeras, TR
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
4.3
作者：
Dinger ME;Pang KC;Mercer TR;Mattick JS
通讯作者：
Mattick JS
影响因子：
4.3
作者：
Glinskii, Anna B.;Ma, Jun;Glinsky, Gennadi V.
通讯作者：
Glinsky, Gennadi V.
影响因子：
56.9
作者：
Kapranov, Philipp;Cheng, Jill;Gingeras, Thomas R.
通讯作者：
Gingeras, Thomas R.